LIVIVO - Search results -

Search results

Result 1 - 10 of total 68

Search options

Article ; Online: Models behind the mystery of establishing enhancer-promoter interactions.

Monfils, Kathryn / Barakat, Tahsin Stefan

2021 Volume 100, Issue 5-6, Page(s) 151170

Abstract: Enhancers and promoters are transcriptional regulatory elements whose facilitated interactions increase gene expression. Enhancer DNA sequences can be located far away from the promoter sequences that they regulate. Currently, the mechanism facilitating ... ...

Abstract	Enhancers and promoters are transcriptional regulatory elements whose facilitated interactions increase gene expression. Enhancer DNA sequences can be located far away from the promoter sequences that they regulate. Currently, the mechanism facilitating the establishment of enhancer-promoter interactions remains unclear. However, mutations causing errors in these interactions have been linked to cancer and disease, further conveying the need to understand the full mechanism. This review discusses multiple models that have been proposed to describe how enhancers go the distance to interact with promoters. Evidence supporting loop formation models is reviewed in addition to more complex hypotheses involving aspects of 3D chromatin organization and phase separation.
MeSH term(s)	Chromatin/genetics ; Enhancer Elements, Genetic/genetics ; Promoter Regions, Genetic
Chemical Substances	Chromatin
Language	English
Publishing date	2021-07-07
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	391967-5
ISSN	1618-1298 ; 0070-2463 ; 0171-9335
ISSN (online)	1618-1298
ISSN	0070-2463 ; 0171-9335
DOI	10.1016/j.ejcb.2021.151170
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 667: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾

Article ; Online: The evolution of Great Apes has shaped the functional enhancers' landscape in human embryonic stem cells.

Glinsky, Gennadi / Barakat, Tahsin Stefan

Stem cell research

2019 Volume 37, Page(s) 101456

Abstract: High-throughput functional assays of enhancer activity have recently enabled the genome-scale definition of molecular, structural, and biochemical features of these genomic regulatory regions. To infer the evolutionary origin of DNA sequences operating ... ...

Abstract	High-throughput functional assays of enhancer activity have recently enabled the genome-scale definition of molecular, structural, and biochemical features of these genomic regulatory regions. To infer the evolutionary origin of DNA sequences operating as functional enhancers in human embryonic stem cells (hESC), we examined the patterns of evolutionary conservation and divergence in the genome-wide functional enhancers' landscape of hESC. We show that a prominent majority (up to 94%) of DNA sequences identified in hESC as functional enhancers are conserved in humans and our closest evolutionary relatives, Chimpanzee and Bonobo. More than 91% of functional enhancers that are highly conserved in both Chimpanzee and Bonobo, are conserved among other Great Apes and >75% are conserved in the Rhesus genome. In striking contrast, <5% of DNA sequences operating in hESC as functional enhancers are conserved in rodents. Conserved in primates enhancers' sequences are complemented by 1619 sequences of enhancers that are specific to humans. Enhancers that harbor human-specific sequences appear enriched among the invariant enhancer module maintaining activity in different pluripotent states and these regions are associated with pluripotency- and embryonic-lineage-related genes. However, functional enhancers make up only a minority of all conserved in primates or human-specific transcription factor binding sites. Our analyses revealed that sequences that are conserved during ~8 million years of primate evolution dominate the genomic landscape of functional enhancers in both primed and naïve hESC. Collectively, these observations revealed thousands of evolutionarily conserved sequences that function as a core regulatory network in human embryonic stem cells which has recently undergone further extension after divergence of modern humans from our closest relatives, Chimpanzee and Bonobo.
MeSH term(s)	Animals ; Enhancer Elements, Genetic ; Evolution, Molecular ; Gene Expression Regulation ; Genomics/methods ; Histones/genetics ; Histones/metabolism ; Hominidae ; Human Embryonic Stem Cells/metabolism ; Humans
Chemical Substances	Histones
Language	English
Publishing date	2019-05-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1876-7753
ISSN (online)	1876-7753
DOI	10.1016/j.scr.2019.101456
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: The non-coding genome in genetic brain disorders: new targets for therapy?

Medico-Salsench, Eva / Karkala, Faidra / Lanko, Kristina / Barakat, Tahsin Stefan

Essays in biochemistry

2022 Volume 65, Issue 4, Page(s) 671–683

Abstract: The non-coding genome, consisting of more than 98% of all genetic information in humans and once judged as 'Junk DNA', is increasingly moving into the spotlight in the field of human genetics. Non-coding regulatory elements (NCREs) are crucial to ensure ... ...

Abstract	The non-coding genome, consisting of more than 98% of all genetic information in humans and once judged as 'Junk DNA', is increasingly moving into the spotlight in the field of human genetics. Non-coding regulatory elements (NCREs) are crucial to ensure correct spatio-temporal gene expression. Technological advancements have allowed to identify NCREs on a large scale, and mechanistic studies have helped to understand the biological mechanisms underlying their function. It is increasingly becoming clear that genetic alterations of NCREs can cause genetic disorders, including brain diseases. In this review, we concisely discuss mechanisms of gene regulation and how to investigate them, and give examples of non-coding alterations of NCREs that give rise to human brain disorders. The cross-talk between basic and clinical studies enhances the understanding of normal and pathological function of NCREs, allowing better interpretation of already existing and novel data. Improved functional annotation of NCREs will not only benefit diagnostics for patients, but might also lead to novel areas of investigations for targeted therapies, applicable to a wide panel of genetic disorders. The intrinsic complexity and precision of the gene regulation process can be turned to the advantage of highly specific treatments. We further discuss this exciting new field of 'enhancer therapy' based on recent examples.
MeSH term(s)	Brain Diseases/drug therapy ; Brain Diseases/genetics ; Gene Expression Regulation ; Genome ; Humans
Language	English
Publishing date	2022-03-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	1744-1358 ; 0071-1365
ISSN (online)	1744-1358
ISSN	0071-1365
DOI	10.1042/EBC20200121
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Solving the unsolved genetic epilepsies: Current and future perspectives.

Johannesen, Katrine M / Tümer, Zeynep / Weckhuysen, Sarah / Barakat, Tahsin Stefan / Bayat, Allan

Epilepsia

2023 Volume 64, Issue 12, Page(s) 3143–3154

Abstract: Many patients with epilepsy undergo exome or genome sequencing as part of a diagnostic workup; however, many remain genetically unsolved. There are various factors that account for negative results in exome/genome sequencing for patients with epilepsy: ( ... ...

Abstract	Many patients with epilepsy undergo exome or genome sequencing as part of a diagnostic workup; however, many remain genetically unsolved. There are various factors that account for negative results in exome/genome sequencing for patients with epilepsy: (1) the underlying cause is not genetic; (2) there is a complex polygenic explanation; (3) the illness is monogenic but the causative gene remains to be linked to a human disorder; (4) family segregation with reduced penetrance; (5) somatic mosaicism or the complexity of, for example, a structural rearrangement; or (6) limited knowledge or diagnostic tools that hinder the proper classification of a variant, resulting in its designation as a variant of unknown significance. The objective of this review is to outline some of the diagnostic options that lie beyond the exome/genome, and that might become clinically relevant within the foreseeable future. These options include: (1) re-analysis of older exome/genome data as knowledge increases or symptoms change; (2) looking for somatic mosaicism or long-read sequencing to detect low-complexity repeat variants or specific structural variants missed by traditional exome/genome sequencing; (3) exploration of the non-coding genome including disruption of topologically associated domains, long range non-coding RNA, or other regulatory elements; and finally (4) transcriptomics, DNA methylation signatures, and metabolomics as complementary diagnostic methods that may be used in the assessment of variants of unknown significance. Some of these tools are currently not integrated into standard diagnostic workup. However, it is reasonable to expect that they will become increasingly available and improve current diagnostic capabilities, thereby enabling precision diagnosis in patients who are currently undiagnosed.
MeSH term(s)	Humans ; Genetic Variation/genetics ; Epilepsy/diagnosis ; Epilepsy/genetics ; Exome ; Exome Sequencing ; Chromosome Mapping
Language	English
Publishing date	2023-10-17
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	216382-2
ISSN	1528-1167 ; 0013-9580
ISSN (online)	1528-1167
ISSN	0013-9580
DOI	10.1111/epi.17780
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 517: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 475: Show issues

Order via subito

Details ▾

Article: Case Report: Two New Cases of Chromosome 12q14 Deletions and Review of the Literature.

Deng, Ruizhi / McCalman, Melysia T / Bossuyt, Thomas P / Barakat, Tahsin Stefan

Frontiers in genetics

2021 Volume 12, Page(s) 716874

Abstract: Interstitial deletions on the long arm of chromosome 12 (12q deletions) are rare, and are associated with intellectual disability, developmental delay, failure to thrive and congenital anomalies. The precise genotype-phenotype correlations of different ... ...

Abstract	Interstitial deletions on the long arm of chromosome 12 (12q deletions) are rare, and are associated with intellectual disability, developmental delay, failure to thrive and congenital anomalies. The precise genotype-phenotype correlations of different deletions has not been completely resolved. Ascertaining individuals with overlapping deletions and complex phenotypes may help to identify causative genes and improve understanding of 12q deletion syndromes. We here describe two individuals with non-overlapping 12q14 deletions encountered at our clinical genetics outpatient clinic and perform a review of all previously published interstitial 12q deletions to further delineate genotype-phenotype correlations. Both individuals presented with a neurodevelopmental disorder with various degrees of intellectual disability, failure to thrive and dysmorphic features. Previously, larger deletions overlapping large parts of the deletions encountered in both individuals have been described. Whereas, individual 1 seems to fit into the previously described phenotypic spectrum of the 12q14 microdeletion syndrome, individual 2 displays more severe neurological symptoms, which are likely caused by haploinsufficiency of the BAF complex member
Language	English
Publishing date	2021-09-01
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2021.716874
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Generation of knockout alleles by RFLP based BAC targeting of polymorphic embryonic stem cells.

Barakat, Tahsin Stefan / Gribnau, Joost

Methods in molecular biology (Clifton, N.J.)

2015 Volume 1227, Page(s) 143–180

Abstract: The isolation of germ line competent mouse Embryonic Stem (ES) cells and the ability to modify the genome by homologous recombination has revolutionized life science research. Since its initial discovery, several approaches have been introduced to ... ...

Abstract	The isolation of germ line competent mouse Embryonic Stem (ES) cells and the ability to modify the genome by homologous recombination has revolutionized life science research. Since its initial discovery, several approaches have been introduced to increase the efficiency of homologous recombination, including the use of isogenic DNA for the generation of targeting constructs, and the use of Bacterial Artificial Chromosomes (BACs). BACs have the advantage of combining long stretches of homologous DNA, thereby increasing targeting efficiencies, with the possibilities delivered by BAC recombineering approaches, which provide the researcher with almost unlimited possibilities to efficiently edit the genome in a controlled fashion. Despite these advantages of BAC targeting approaches, a widespread use has been hampered, mainly because of the difficulties in identifying BAC-targeted knockout alleles by conventional methods like Southern Blotting. Recently, we introduced a novel BAC targeting strategy, in which Restriction Fragment Length Polymorphisms (RFLPs) are targeted in polymorphic mouse ES cells, enabling an efficient and easy PCR-based readout to identify properly targeted alleles. Here we provide a detailed protocol for the generation of targeting constructs, targeting of ES cells, and convenient PCR-based analysis of targeted clones, which enable the user to generate knockout ES cells of almost every gene in the mouse genome within a 2-month period.
MeSH term(s)	Alleles ; Animals ; Chromosomes, Artificial, Bacterial/chemistry ; Chromosomes, Artificial, Bacterial/metabolism ; Electroporation ; Embryo, Mammalian ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/metabolism ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Fibroblasts/cytology ; Fibroblasts/metabolism ; Gene Targeting/methods ; Genetic Vectors/chemistry ; Genetic Vectors/metabolism ; Genome ; Genomic Library ; Homologous Recombination ; Mice ; Mice, Knockout ; Plasmids/chemistry ; Plasmids/metabolism ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length
Language	English
Publishing date	2015
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-1652-8_7
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: Beyond the Exome: The Non-coding Genome and Enhancers in Neurodevelopmental Disorders and Malformations of Cortical Development.

Perenthaler, Elena / Yousefi, Soheil / Niggl, Eva / Barakat, Tahsin Stefan

Frontiers in cellular neuroscience

2019 Volume 13, Page(s) 352

Abstract: The development of the human cerebral cortex is a complex and dynamic process, in which neural stem cell proliferation, neuronal migration, and post-migratory neuronal organization need to occur in a well-organized fashion. Alterations at any of these ... ...

Abstract	The development of the human cerebral cortex is a complex and dynamic process, in which neural stem cell proliferation, neuronal migration, and post-migratory neuronal organization need to occur in a well-organized fashion. Alterations at any of these crucial stages can result in malformations of cortical development (MCDs), a group of genetically heterogeneous neurodevelopmental disorders that present with developmental delay, intellectual disability and epilepsy. Recent progress in genetic technologies, such as next generation sequencing, most often focusing on all protein-coding exons (e.g., whole exome sequencing), allowed the discovery of more than a 100 genes associated with various types of MCDs. Although this has considerably increased the diagnostic yield, most MCD cases remain unexplained. As Whole Exome Sequencing investigates only a minor part of the human genome (1-2%), it is likely that patients, in which no disease-causing mutation has been identified, could harbor mutations in genomic regions beyond the exome. Even though functional annotation of non-coding regions is still lagging behind that of protein-coding genes, tremendous progress has been made in the field of gene regulation. One group of non-coding regulatory regions are enhancers, which can be distantly located upstream or downstream of genes and which can mediate temporal and tissue-specific transcriptional control via long-distance interactions with promoter regions. Although some examples exist in literature that link alterations of enhancers to genetic disorders, a widespread appreciation of the putative roles of these sequences in MCDs is still lacking. Here, we summarize the current state of knowledge on
Language	English
Publishing date	2019-07-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2019.00352
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Confirmation and expansion of the phenotype of the TCEAL1-related neurodevelopmental disorder.

Albuainain, Fatimah / Shi, Yuwei / Lor-Zade, Sarah / Hüffmeier, Ulrike / Pauly, Melissa / Reis, André / Faivre, Laurence / Maraval, Julien / Bruel, Ange-Line / Them, Frédéric Tran Mau / Haack, Tobias B / Grasshoff, Ute / Horber, Veronka / Schot, Rachel / van Slegtenhorst, Marjon / Wilke, Martina / Barakat, Tahsin Stefan

European journal of human genetics : EJHG

2024 Volume 32, Issue 3, Page(s) 350–356

Abstract: Numerous contiguous gene deletion syndromes causing neurodevelopmental disorders have previously been defined using cytogenetics for which only in the current genomic era the disease-causing genes have become elucidated. One such example is deletion at ... ...

Abstract	Numerous contiguous gene deletion syndromes causing neurodevelopmental disorders have previously been defined using cytogenetics for which only in the current genomic era the disease-causing genes have become elucidated. One such example is deletion at Xq22.2, previously associated with a neurodevelopmental disorder which has more recently been found to be caused by de novo loss-of-function variants in TCEAL1. So far, a single study reported six unrelated individuals with this monogenetic disorder, presenting with syndromic features including developmental delay especially affecting expressive speech, intellectual disability, autistic-like behaviors, hypotonia, gait abnormalities and mild facial dysmorphism, in addition to ocular, gastrointestinal, and immunologic abnormalities. Here we report on four previously undescribed individuals, including two adults, with de novo truncating variants in TCEAL1, identified through trio exome or genome sequencing, further delineating the phenotype of the TCEAL1-related disorder. Whereas overall we identify similar features compared to the original report, we also highlight features in our adult individuals including hyperphagia, obesity, and endocrine abnormalities including hyperinsulinemia, hyperandrogenemia, and polycystic ovarian syndrome. X chromosome inactivation and RNA-seq studies further provide functional insights in the molecular mechanisms. Together this report expands the phenotypic and molecular spectrum of the TCEAL1-related disorder which will be useful for counseling of newly identified individuals and their families.
MeSH term(s)	Adult ; Female ; Humans ; Neurodevelopmental Disorders/genetics ; Intellectual Disability/genetics ; Autistic Disorder/genetics ; Base Sequence ; Phenotype ; DNA-Binding Proteins/genetics ; Transcription Factors/genetics
Chemical Substances	TCEAL1 protein, human ; DNA-Binding Proteins ; Transcription Factors
Language	English
Publishing date	2024-01-10
Publishing country	England
Document type	Journal Article
ZDB-ID	1141470-4
ISSN	1476-5438 ; 1018-4813
ISSN (online)	1476-5438
ISSN	1018-4813
DOI	10.1038/s41431-023-01530-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 3589: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: The Why of YY1: Mechanisms of Transcriptional Regulation by Yin Yang 1.

Verheul, Thijs C J / van Hijfte, Levi / Perenthaler, Elena / Barakat, Tahsin Stefan

Frontiers in cell and developmental biology

2020 Volume 8, Page(s) 592164

Abstract: First described in 1991, Yin Yang 1 (YY1) is a transcription factor that is ubiquitously expressed throughout mammalian cells. It regulates both transcriptional activation and repression, in a seemingly context-dependent manner. YY1 has a well- ... ...

Abstract	First described in 1991, Yin Yang 1 (YY1) is a transcription factor that is ubiquitously expressed throughout mammalian cells. It regulates both transcriptional activation and repression, in a seemingly context-dependent manner. YY1 has a well-established role in the development of the central nervous system, where it is involved in neurogenesis and maintenance of homeostasis in the developing brain. In neurodevelopmental and neurodegenerative disease, the crucial role of YY1 in cellular processes in the central nervous system is further underscored. In this mini-review, we discuss the various mechanisms leading to the transcriptional activating and repressing roles of YY1, including its role as a traditional transcription factor, its interactions with cofactors and chromatin modifiers, the role of YY1 in the non-coding genome and 3D chromatin organization and the possible implications of the phase-separation mechanism on YY1 function. We provide examples on how these processes can be involved in normal development and how alterations can lead to various diseases.
Language	English
Publishing date	2020-09-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2020.592164
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Combined DNA-RNA fluorescent in situ hybridization (FISH) to study X chromosome inactivation in differentiated female mouse embryonic stem cells.

Barakat, Tahsin Stefan / Gribnau, Joost

Journal of visualized experiments : JoVE

2014 , Issue 88

Abstract: Fluorescent in situ hybridization (FISH) is a molecular technique which enables the detection of nucleic acids in cells. DNA FISH is often used in cytogenetics and cancer diagnostics, and can detect aberrations of the genome, which often has important ... ...

Abstract	Fluorescent in situ hybridization (FISH) is a molecular technique which enables the detection of nucleic acids in cells. DNA FISH is often used in cytogenetics and cancer diagnostics, and can detect aberrations of the genome, which often has important clinical implications. RNA FISH can be used to detect RNA molecules in cells and has provided important insights in regulation of gene expression. Combining DNA and RNA FISH within the same cell is technically challenging, as conditions suitable for DNA FISH might be too harsh for fragile, single stranded RNA molecules. We here present an easily applicable protocol which enables the combined, simultaneous detection of Xist RNA and DNA encoded by the X chromosomes. This combined DNA-RNA FISH protocol can likely be applied to other systems where both RNA and DNA need to be detected.
MeSH term(s)	Animals ; Cell Differentiation/genetics ; DNA/analysis ; Embryonic Stem Cells/physiology ; Female ; In Situ Hybridization, Fluorescence/methods ; Mice ; RNA/analysis ; X Chromosome Inactivation
Chemical Substances	RNA (63231-63-0) ; DNA (9007-49-2)
Language	English
Publishing date	2014-06-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/51628
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito